The Viral Epidemiology Branch (VEB) has used a variety of approaches to define the nature and magnitude of HIV-1 associated malignancies, including analyses of population- based data, prospective cohort studies, and laboratory investigations. Our current work has focused on Kaposis sarcoma and its associated herpesvirus, HHV-8. We have measured T-cell proliferative response to this infection and found evidence for cellular immunity; these responses were diminished in the presence of HIV infection, even with intact levels of CD4+ T-cells, which parallels the early increase in Kaposi?s sarcoma risk following HIV seroconversion. Using HHV- 8 serologic assays on banked blood specimens, VEB researchers identified pre-existing HHV-8 infection as a cause of transplant associated Kaposi?s sarcoma. In a collaborative work, we found that polymorphisms in HHV-8 latent nuclear antigen define a large repertoire of viral genotypes in the infected population, which may prove useful in defining the molecular epidemiology of this infection. We have used serologic assays to examine HHV-8 seroprevalence in various populations, and found low seroprevalence in Southeast Asia and the Caribbean, and high prevalence in African populations. In collaborative studies in Jamaica and Zambia, we determined that HHV-8 seroprevalence increases progressively with age. We also collaborated on a clinical trial which demonstrated potential efficacy of anti-angiogenic therapy in Kaposis sarcoma. - Human Subjects & Human Subjects: Minor under 18 Years Old & Human Subjects: Interview, Questionaires, or Surveys Only & Human Tissues, Fluids, Cells, etc.